# Clinical Evidence of Wearable-Derived Heart Rate Variability for Detecting Systemic Inflammation: A Systematic Review

**Authors:** Rukmono Siswishanto, Detty Siti Nurdiati, Irwan Endrayanto Aluicius, Aulia Ichlasul Rezza, Dean Batrisha

PMC · DOI: 10.3390/diagnostics16040538 · 2026-02-11

## TL;DR

This paper reviews clinical studies to determine if wearable heart rate variability (HRV) can detect systemic inflammation, finding mixed but promising results.

## Contribution

The study systematically evaluates HRV's clinical relevance as a non-invasive biomarker for systemic inflammation using wearable devices.

## Key findings

- SDNN from ECG-based wearables shows consistent inverse association with CRP in 83% of cases.
- RMSSD and inflammatory cytokines show heterogeneous and largely non-significant associations.
- ECG-based devices yield more consistent results than photoplethysmography-based ones.

## Abstract

Background/Objectives: Wearable devices capable of capturing heart rate variability (HRV) enable continuous assessment of autonomic nervous system function in real-world settings. Because systemic inflammation disrupts autonomic balance through vagal withdrawal and sympathetic activation, HRV has been proposed as a non-invasive digital biomarker of inflammatory activity. Despite the rapid expansion of wearable sensor technologies, the accuracy and consistency for detecting systemic inflammatory states remain unclear. This systematic review aimed to evaluate the clinical relevance of wearable-derived HRV indices in relation to established inflammatory biomarkers. Methods: A systematic search of PubMed, Scopus, Web of Science, and the Cochrane Library was conducted through April 2025. Due to methodological heterogeneity, findings were synthesized using the Synthesis Without Meta-analysis (SWiM) framework with vote counting, effect-direction plots, and sign tests. Results: Eleven studies involving 2419 participants met the inclusion criteria. Vote counting demonstrated that SDNN showed a predominantly inverse association with CRP, with 83% of comparisons indicating reduced SDNN in the presence of elevated CRP (sign test p = 0.031). In contrast, associations between RMSSD and inflammatory cytokines were heterogeneous and largely non-significant. ECG-based wearable devices yielded more consistent associations than photoplethysmography-based devices, while recording duration and population characteristics contributed to variability across studies. Conclusions: Wearable-derived HRV, particularly SDNN from ECG-based devices, shows a consistent inverse association with CRP, supporting its role as a non-invasive physiological correlate of systemic inflammation. However, heterogeneity and the lack of diagnostic accuracy metrics limit conclusions regarding clinical utility. At present, wearable HRV should be considered an exploratory or adjunctive biomarker, pending validation in standardized longitudinal studies with formal diagnostic performance assessment.

## Full-text entities

- **Genes:** IL1RN (interleukin 1 receptor antagonist) [NCBI Gene 3557] {aka CRMO2, DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, LGALS3 (galectin 3) [NCBI Gene 3958] {aka CBP35, GAL3, GALBP, GALIG, L31, LGALS2}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}
- **Diseases:** ulcerative colitis (MESH:D003093), HIV infection (MESH:D015658), cardiovascular autonomic disorders (MESH:D018376), Systemic (MESH:D015619), heart disease (MESH:D006331), inflammatory bowel disease (MESH:D015212), AVNRT (MESH:D013611), infections (MESH:D007239), cardiovascular conditions (MESH:D002318), COVID-19 (MESH:D000086382), hypertension (MESH:D006973), epilepsy (MESH:D004827), endotoxemia (MESH:D019446), PPROMs (MESH:C563032), autoimmune disorders (MESH:D001327), obesity (MESH:D009765), RMSSD (MESH:D011843), traumatic brain injury (MESH:D000070642), injury to (MESH:D014947), Inflammation (MESH:D007249), metabolic syndrome (MESH:D024821)
- **Chemicals:** lipopolysaccharide (MESH:D008070), catecholamine (MESH:D002395)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12939863/full.md

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Source: https://tomesphere.com/paper/PMC12939863